This Transition Center PSO application is a continuation of the Neuroscience COBRE at the University of Wyoming (UW). The Center goals were to develop a critical mass of neuroscience faculty, foster biomedical research in neurological disorders, increase NIH funding at UW, establish a Career Mentoring program, and develop the required research infrastructure, specifically the Microscopy Core. These goals have been met and the success of the Neuroscience Center and the development of the Microscopy Core is directly attributable to the NCRR COBRE grant, and secondly to the significant institutional commitment. UW provided 7 state-funded, tenure track neuroscience positions to the Center and state funding for the Microscopy Core Director. The Microscopy Core is essential to the success of the Neuroscience Center investigators and additional biomedical researchers on campus. The Core Director provides technical guidance in the use of the optical and electron microscopes in the facility. The Microscopy Core has enabled investigators to identify how normal synaptic connections are formed and the effects of protein misfolding on neuronal morphology in neurodegeneration. The Phase III grant will support Career Development, Pilot Research Projects (for assembling preliminary data for grants), and the Microscopy Core. Plans to sustain the Core following the completion of the Phase III transition grant are identified. Research progress of Center investigators has led to new hypotheses and experimental questions pertaining to how nervous system morphology and function changes with the life-stage, disease, experience, and experimental manipulation. The Neuroscience Center will provide the structure for building innovative and productive collaborations that address major biomedical issues related to mechanisms of synaptic plasticity, neurodegeneration, and chronic pain. Prion diseases are a prototypic protein misfolding disease and they share many molecular and pathological features with the more frequent human neurodegenerative disorders, e.g. Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). New collaborative projects are identified that will utilize model systems that enable us to bridge between protein misfolding pathways and the downstream functional effects on neuronal activity and brain circuits, and common ways for therapeutic intervention.